The proposed research will investigate the process by which mammalian growth is controlled by homocysteine derivatives, including homocysteic acid, the macromolecular changes produced by homocysteine and sulfate in the proteoglycans synthesized by cultured connective tissue cells, the metabolic conversion of methionine and homocysteine to homocysteic acid in liver, the relationship of sulfation of proteoglycans to contact inhibition in transformed cells in culture, and the metabolic macromolecular changes by which homocysteinemia produces accelerated arteriosclerosis.